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1.

Background

Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.

Material and Methods

IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.

Results

160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).

Conclusion

Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer.  相似文献   

2.

Background

The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.

Material and Methods

In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines.

Results

Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line.

Conclusions

Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer.  相似文献   

3.

Objective

The objective of this study was to perform a meta-analysis of published studies for evaluating the impact of neoadjuvant chemotherapy (NAC) on immediate breast reconstruction.

Methods

We searched medical databases to identify appropriate studies that assessed the impact of NAC on immediate breast reconstruction from the inception of this technique through April 2013. We then performed a meta-analysis of these studies.

Results

Our searches identified 11 studies among 1,840 citations. In the meta-analysis, NAC did not increase the overall rate of complications after immediate breast reconstruction (odds ratio [OR] = 0.59; 95% confidence interval[CI] = 0.38–0.91). The complication rate was also unaffected by NAC when we considered infections (OR = 0.82; 95% CI = 0.46–1.45), hematomas (OR = 1.35; 95% CI = 0.57–3.21), and seromas (OR = 0.77; 95% CI = 0.23–2.55). Additionally, expander or implant loss did not significantly increase in patients after NAC (OR = 1.59; 95% CI = 0.91–2.79). Only 2 studies (202 procedures) had reported total autologous flap loss, and they were included in our analysis; both studies found no association between NAC and total flap loss.

Conclusion

Our analysis suggests that NAC does not increase the complication rate after immediate breast reconstruction. For appropriately selected patients, immediate breast reconstruction following NAC is a safe procedure. The best way to study this issue in the future is to conduct a multicenter prospective study with a longer follow-up period and more clearly defined parameters.  相似文献   

4.

Background

The prognostic effect of tumor infiltrating CD8+ cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8+ CTLs and survival of untreated node-negative breast cancer patients.

Material and Methods

CD8+ CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8+ CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status.

Results

285 (85.8%) patients showed strong CD8+ CTLs infiltrate positive status. Univariate analysis showed that CD8+ CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265–0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220–0.840) in the entire cohort. The significance of CD8+ CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8+ CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242–0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202–0.797).  相似文献   

5.

Background

The efficacy of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of sorafenib for treating patients with advanced HCC.

Methods

The PubMed, Embase, and Web of Science databases were searched. Eligible studies were randomized controlled trials (RCTs) that assessed sorafenib therapy in patients with advanced HCC. The outcomes included overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicities. Hazard ratio (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).

Results

Seven RCTs, with a total of 3807 patients, were included in this meta-analysis. All patients received sorafenib alone, or with other chemotherapeutic regimens. Pooled estimates showed that sorafenib improved the OS (HR = 0.74, 95% CI: 0.61, 0.90; P = 0.002), or TTP outcomes (HR = 0.69, 95% CI: 0.55, 0.86; P = 0.001). Subgroup analysis revealed that sorafenib was more effective in the patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1–2 (HR = 0.77, 95% CI: 0.60, 1.0; P = 0.05), or macroscopic vascular invasion (MVI), and/or extrahepatic spread (EHS) (HR = 0.65, 95% CI: 0.46, 0.93; P = 0.02), in terms of OS. Patients who received sorafenib did not have a higher ORR (RR = 0.85, 95% CI: 0.65, 1.11; P = 0.10). In addition, there was a slight increase in toxicity in the sorafenib group.

Conclusion

Treatment with sorafenib significantly improved OS and TTP in patients with advanced HCC. Additional large-scale, well-designed RCTs are needed to evaluate the efficacy of sorafenib-based therapy in the treatment of advanced HCC.  相似文献   

6.

Objective

The role of BRCA dysfunction on the prognosis of patients with epithelial ovarian cancer (EOCs) remains controversial. This systematic review tried to assess the role of BRCA dysfunction, including BRCA1/2 germline, somatic mutations, low BRCA1 protein/mRNA expression or BRCA1 promoter methylation, as prognostic factor in EOCs.

Methods

Studies were selected for analysis if they provided an independent assessment of BRCA status and prognosis in EOC. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a modified quality scale.

Results

Of 35 evaluable studies, 23 identified BRCA dysfucntion status as a favourable prognostic factor. No significant differences were detected in the global score of quality assessment. The aggregated hazard ratio (HR) of overall survival (OS) of 34 evaluable studies suggested that BRCA dysfunction status had a favourable impact on OS (HR = 0.69, 95% CI 0.61–0.79), and when these studies were categorised into BRCA1/2 mutation and low protein/mRNA expression of BRCA1 subgroups, all of them demonstrated positive results (HR = 0.67, 95% CI: 0.57–0.78; HR = 0.62, 95% CI: 0.51–0.75; and HR = 0.51, 95% CI: 0.33–0.78, respectively), except for the subgroup of BRCA1 promoter methylation (HR = 1.59, 95% CI: 0.72–3.50). The meta-analysis of progression-free survival (PFS), which included 18 evaluable studies, demonstrated that BRCA dysfunction status was associated with a longer PFS in EOC (HR = 0.69, 95% CI: 0.63–0.76).

Conclusions

Patients with BRCA dysfunction status tend to have a better outcome, but further prospective clinical studies comparing the different BRCA statuses in EOC is urgently needed to specifically define the most effective treatment for the separate patient groups.  相似文献   

7.

Background

Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers.

Methods

We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000–2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women''s characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes.

Results

A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28–3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24–12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59–3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60–2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23–2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58–9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18–2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00–2.49).

Conclusion

The role of women''s characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.  相似文献   

8.

Background

To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.

Methods

A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.

Results

Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.

Conclusion

Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.  相似文献   

9.

Background

Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.

Methodology

Eligible studies were searched from the PubMed, Embase and Web of Science databases. Correlation between E-cadherin expression and clinicopathological features and prognosis was analyzed. Subgroup analysis was also performed according to study location, number of patients, quality score of studies and cut-off value.

Principal Findings

A total of 27 studies comprising 4244 cases met the inclusion criteria. Meta-analysis suggested that downregulated E-cadherin expression had an unfavorable impact on overall survival (OS) of CRC (n = 2730 in 14 studies; HR = 2.27, 95%CI: 1.63–3.17; Z = 4.83; P = 0.000). Subgroup analysis indicated that low E-cadherin expression was significantly associated with worse OS in Asian patients (n = 1054 in 9 studies; HR = 2.86, 95%CI: 2.13–3.7, Z = 7.11; P = 0.000) but not in European patients (n = 1552 in 4 studies; HR = 1.14, 95%CI: 0.95–1.35, Z = 1.39; P = 0.165). In addition, reduced E-cadherin expression indicated an unfavorable OS only when the cut off value of low E-cadherin expression was >50% (n = 512 in 4 studies; HR = 2.08, 95%CI 1.45–2.94, Z = 4.05; P = 0.000). Downregulated E-cadherin expression was greatly related with differentiation grade, Dukes'' stages, lymphnode status and metastasis. The pooled OR was 0.36(95%CI: 0.19–0.7, Z = 3.03, P = 0.002), 0.34(95%CI: 0.21–0.55, Z = 6.61, P = 0.000), 0.49(95%CI: 0.32–0.74, Z = 3.02, P = 0.002) and 0.45(95%CI: 0.22–0.91, Z = 3.43, P = 0.001), respectively.

Conclusions

This study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC. However, downregulated E-cadherin expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients. Additionally, this meta-analysis suggested that the negative threshold of E-cadherin should be >50% when we detected its expression in the immunohistochemistry stain.  相似文献   

10.

Background

An elevated preoperative neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic factor for hepatocellular carcinoma (HCC) patients after treatment. However, the clinical implication of postoperative NLR change remains unclear.

Materials and Methods

From May 2005 to Aug 2008, a cohort of consecutive 178 small HCC patients treated with radiofrequency ablation (RFA) was retrospectively reviewed. The NLR was recorded within 3 days before and 1 month after RFA. Baseline characteristics, overall survival (OS) and recurrence free survival (RFS) were compared according to preoperative NLR and/or postoperative NLR change. Prognostic factors were assessed by multivariate analysis.

Results

Compared with preoperative NLR level, postoperative NLR decreased in 87 patients and increased in 91 patients after RFA. No significant differences were identified between two groups in commonly used clinic-pathologic features. The 1, 3, 5 years OS was 98.8%, 78.6%, 67.1% for NLR decreased group, and 92.2%, 55.5%, 35.4% for NLR increased group respectively (P<0.001); the corresponding RFS was 94.2%, 65.2%, 33.8% and 81.7%, 46.1%, 12.4% respectively (P<0.001). In subgroup analysis, the survival of patients with lower or higher preoperative NLR can be distinguished more accurate by postoperative NLR change. Multivariate analysis showed that postoperative NLR change, but not preoperative NLR, was an independent prognostic factor for both OS (P<0.001, HR = 2.39, 95%CI 1.53–3.72) and RFS (P = 0.003, HR = 1.69, 95%CI 1.87–8.24).

Conclusion

The postoperative NLR change was an independent prognostic factor for small HCC patient undergoing RFA, and patients with decreased NLR indicated better survival than those with increased NLR.  相似文献   

11.

Purpose

Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making.

Patients and Methods

A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors.

Results

Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016).

Conclusion

In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse.  相似文献   

12.

Background

The aim of the present study was to investigate potential risk factors for synchronous bilateral breast cancer sBBC).

Methods

A retrospective analysis was performed of patients diagnosed and treated with operable bilateral breast cancer (BBC) between June 2007 and December 2011. Risk factors for sBBC were evaluated in this cohort and further validated in a prospective observational validation analysis of patients between January 2012 and December 2012. Patients treated with operable unilateral breast cancer during the same period were used as a control group.

Results

A total of 11,247 patients with primary breast cancer underwent operations at the Fudan University Shanghai Cancer Center between June 2007 and December 2012. The incidence of sBBC was 1.6%. The age at diagnosis (HR = 2.4, 95% C.I.: 1.4–4.0, p = 0.001), presence of sclerosing adenosis (HR = 11.8, 95% C.I.: 5.3–26.3, p<0.001), lobular carcinoma component involvement (HR = 5.6, 95% C.I.: 2.6–12.1, p<0.001), and family history of first-degree relatives with breast cancer (HR = 2.0, 95% C.I.: 1.1–3.4, p<0.001) were independent risk factors for sBBC. A subsequent validation study failed to confirm the significance of family history. No significant difference on survival was found between patients with early-stage sBBC and control cases.

Conclusions

Patients with the presence of sclerosing in the affected breast, and lobular carcinoma component involvement may be at high risk for developing sBBC. This study supports the hypothesis that the host-carcinoma biological relationship, especially for the tumor microenvironment, played a critical role in the carcinogenesis of sBBC.  相似文献   

13.

Background

HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients.

Methods

Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials.

Principal Findings

HER2-genes CN strongly correlated to each other (Spearman’s rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1–3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS).

Conclusions

TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis.  相似文献   

14.

Purpose

Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial.

Experimental Design

We conducted a meta-analysis of 55 studies (n = 8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS). The impact of M1 and M2 type TAM (n = 5) on survival was also examined.

Results

High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR)  = 1.20 (95% confidence interval (CI), 1.14–1.28)] and bladder cancer [RR = 3.30 (95%CI, 1.56–6.96)] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35–0.77)]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24–2.16)], breast cancer [RR = 8.62 (95%CI, 3.10–23.95)], bladder cancer [RR = 5.00 (95%CI, 1.98–12.63)], ovarian cancer [RR = 2.55 (95%CI, 1.60–4.06)], oral cancer [RR = 2.03 (95%CI, 1.47–2.80)] and thyroid cancer [RR = 2.72 (95%CI, 1.26–5.86)],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43–0.96)]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival.

Conclusions

Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.  相似文献   

15.

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×109/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×109/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.  相似文献   

16.

Background

Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1–pT2, pN0) breast cancer patients.

Methods

456 patients treated in 1995–1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed.

Results

All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5–191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8–4.8), p<10e−06] and HG3 [HR = 4.4 (2.2–8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5–4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01–4.8), p = 0.04].

Conclusions

We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1–pT2, pN0, breast cancers.  相似文献   

17.

Purpose

We examined individual-level and neighborhood-level predictors of mortality in CRC patients diagnosed in Florida to identify high-risk groups for targeted interventions.

Methods

Demographic and clinical data from the Florida Cancer Data System registry (2007–2011) were linked with Agency for Health Care Administration and US Census data (n = 47,872). Cox hazard regression models were fitted with candidate predictors of CRC survival and stratified by age group (18–49, 50–64, 65+).

Results

Stratified by age group, higher mortality risk per comorbidity was found among youngest (21%), followed by middle (19%), and then oldest (14%) age groups. The two younger age groups had higher mortality risk with proximal compared to those with distal cancer. Compared with private insurance, those in the middle age group were at higher death risk if not insured (HR = 1.35), or received healthcare through Medicare (HR = 1.44), Medicaid (HR = 1.53), or the Veteran’s Administration (HR = 1.26). Only Medicaid in the youngest (52% higher risk) and those not insured in the oldest group (24% lower risk) were significantly different from their privately insured counterparts. Among 18–49 and 50–64 age groups there was a higher mortality risk among the lowest SES (1.17- and 1.23-fold higher in the middle age and 1.12- and 1.17-fold higher in the older age group, respectively) compared to highest SES. Married patients were significantly better off than divorced/separated (HR = 1.22), single (HR = 1.29), or widowed (HR = 1.19) patients.

Conclusion

Factors associated with increased risk for mortality among individuals with CRC included being older, uninsured, unmarried, more comorbidities, living in lower SES neighborhoods, and diagnosed at later disease stage. Higher risk among younger patients was attributed to proximal cancer site, Medicaid, and distant disease; however, lower SES and being unmarried were not risk factors in this age group. Targeted interventions to improve survivorship and greater social support while considering age classification may assist these high-risk groups.  相似文献   

18.

Background

Socio-demographic factors and area of residence might influence the development of esophageal and gastric cancer. Large-scale population-based research can determine the role of such factors.

Methods

This population-based cohort study included all Swedish residents aged 30–84 years in 1990–2007. Educational level, marital status, place of birth, and place of residence were evaluated with regard to mortality from esophageal or gastric cancer. Cox regression yielded hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounding.

Results

Among 84 920 565 person-years, 5125 and 12 230 deaths occurred from esophageal cancer and gastric cancer, respectively. Higher educational level decreased the HR of esophageal cancer (HR = 0.61, 95%CI 0.42–0.90 in women, HR = 0.71, 95%CI 0.60–0.84 in men) and gastric cancer (HR = 0.80, 95%CI 0.63–1.03 in women, HR = 0.73, 95%CI 0.64–0.83 in men). Being unmarried increased HR of esophageal cancer (HR = 1.64, 95%CI 1.35–1.99 in women, HR = 1.64, 95%CI 1.50–1.80 in men), but not of gastric cancer. Being born in low density populated areas increased HR of gastric cancer (HR = 1.23, 95%CI 1.10–1.38 in women, HR = 1.37, 95%CI 1.25–1.50 in men), while no strong association was found with esophageal cancer. Living in densely populated areas increased HR of esophageal cancer (HR = 1.31, 95%CI 1.14–1.50 in women, HR = 1.40, 95%CI 1.29–1.51 in men), but not of gastric cancer.

Conclusion

These socio-demographic inequalities in cancer mortality warrant efforts to investigate possible preventable mechanisms and to promote and support healthier lifestyles among deprived groups.  相似文献   

19.

Background

A number of studies have examined the relationship between the expression of the class III β-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy.

Methods

A literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy.

Results

A total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16–0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27–1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24–1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy).

Conclusions

The expression level of TUBB3 may be a useful biomarker to predict the clinical outcomes of the taxane/vinorebine-based chemotherapy in patients with NSCLC.  相似文献   

20.

Introduction

Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.

Patients and Methods

We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).

Results

Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).

Conclusion

IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.  相似文献   

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